intravenous thrombolysis with rhtnk-tpa for acute non-large vessel occlusion in extended time window

Conditions: Acute Ischemic Stroke

Summary: this study is designed to evaluate the efficacy of iv rhtnk-tpa between 4.5 to 24 hours from symptom onset in patients presenting with a non-large vessel occlusion ischemic stroke.

option is a multicenter, prospective, randomized, open-label, blinded end-point (probe) controlled trial of thrombolysis with rhtnk-tpa versus standard of care. a total of 568 patients will be enrolled at approximately 40 centers around china.

Eligibility criteria:
inclusion criteria: * clinical diagnosis of acute ischemic stroke * age≥18 years * pre-stroke mrs score≤1 points * disabling stroke defined as follows: * baseline nihss score 6-25 at the time of randomization, * or nihss 4-5 with disabling deficit (e.g. hemianopia, aphasia, loss of hand function) as determined by the managing clinician * onset (last-seen-well) time to treatment time between 4.5 and 24 hours * written informed consent from patients or legally responsible representatives * the presence of a target mismatch on ct perfusion: ischemic core volume\ 6 sec lesion/core volume lesion), mismatch volume≥10ml exclusion criteria: * treatment with a thrombolytic within the last 72 hours or intention to receive intravenous thrombolysis * contraindication to thrombolysis * planned or anticipated treatment with endovascular therapy * rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in a nihss score\<4 at randomization * pregnancy or lactating; formal testing needed in women of childbearing potential * brain tumor (with mass effect) * hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency * impairment in coagulation due to comorbid disease or anticoagulant use. if on warfarin, international normalized ratio (inr) \>1.7 or prothrombin time \>15s; if use of any direct oral anticoagulant within the last 48 hours; if use of heparin/heparinoid within the last 24 hours * use of glycoprotein ⅱb-ⅲa inhibitors within the last 72 hours * baseline platelet count \<100,000/μl * undergoing hemodialysis or peritoneal dialysis; known severe renal insufficiency with glomerular filtration rate \ 220mmol/l (2.5mg/dl) * suspected aortic dissection * major surgery or biopsy within the last 1 month * any active bleeding within the previous 1 month (including gastrointestinal or urinary bleeding) * known severe, life-threatening allergy (more severe than skin rash) to contrast agents * severe, uncontrolled hypertension (systolic blood pressure \>185mmhg or diastolic blood pressure \>110mmhg) * any terminal illness such that the patient would not be expected to survive more than half a year * current participation in any investigational study that may confound outcome assessment of the study * any condition that, in the judgement of the investigator, is inappropriate for participation in the trial or could impose hazards to the patient (e.g. inability to understand and/or follow the study procedures and/or follow-up due to mental disorders, cognitive or emotional disorders) specific neuroimaging exclusion criteria: * evidence of acute intracranial hemorrhage * acute large vessel occlusion on magnetic resonance/ computed tomography angiography, including internal carotid artery (ica), middle cerebral artery m1 segment (mca-m1）, vertebral artery and basilar artery

Keywords: acute ischemic stroke extended time window non-large vessel occlusion intravenous thrombolysis